Ache? Pain? Sprain?

Which pill works best for what ails you? With more than 75 percent of us taking over-the-counter painkillers at least once a month (per a Self.com poll), it's key to know the safest and most effective choice.

Acetaminophen (found in Tylenol)

Best for:

Fever

Mild to moderate musculoskeletal pain

Mild to moderate back pain

Mild to moderate headache

Pain-signal reducer

How it functions isn’t well understood, but acetaminophen may block COX-3, a protein that helps send out the body’s pain signals. It’s not as potent as some other OTC painkillers such as naproxen and ibuprofen, so it’s typically effective only for low-intensity aches. If you’ve had alcohol in the past 24 hours (or plan to), hit the brakes: Too much acetaminophen and alcohol can damage the liver. An advisory committee to the FDA has proposed lowering the maximum daily dose from 4 grams (which may be too much for some people); watch these pages for the new limit. If you feel weak or “off” after use, see a doc, stat.

Aspirin (found in Bayer and Anacin)

Best for:

Mild toothache

Moderately sore muscles

Mild to moderate back pain

Mild to moderate headache

Blood declutterer

Aspirin eases pain and inflammation by slowing the production of prostaglandins, molecules that activate pain receptors. The active ingredient, acetylsalicylic acid, also makes blood platelets less sticky, which is why people at risk for heart attack take aspirin to help prevent clots. In many people, acetylsalicylic acid reaches toxicity faster than do ibuprofen and naproxen (the maximum daily dose is 4 grams), so regular use has a higher risk for side effects such as gastric irritation. Thus aspirin is useful for mild to moderate, but not severe or chronic, pain. If you just had or are about to have surgery, steer clear.

Ibuprofen (found in Advil) and naproxen (found in Aleve)

Best for:

Acute muscle injury

Arthritis

Joint pain

Lower-back pain

Moderate to severe headache

Moderate to severe menstrual cramps

Anti-inflammatories

Like aspirin, ibuprofen and naproxen inhibit prostaglandin production to stop inflammation and pain. But they can also disrupt H2, a gut histamine, stimulating the overproduction of gastric acid and leading to stomach upset and even bleeding, warns Rollin M. Gallagher, M.D., of Philadelphia, past president of the American Academy of Pain Medicine. If you have a history of stomach problems (like ulcers), these might not be for you. Call your doc if you have stomach pain, vomiting or black stools or if you cough blood after taking one. The max daily dose for ibuprofen is 1,200 milligrams; for naproxen, 600 mg.

The most important rule

Listen to your body! An OTC pill that works well for one person may not help another, so trial and error can be your best pal. One caveat for pregnant ladies: Ibuprofen, aspirin and naproxen can cause heart problems in the fetus, so consult your M.D. before you take any pill.